Chromatography is a process used in chemical and biochemical research and process control wherein mixtures of chemical compounds are separated into the components of the mixture so that the existence and quantity of each component can be determined. Chromatography is used, for example, in the pharmaceutical industries in basic research, product development, manufacturing, and quality control. In the high pressure (or performance) liquid chromatography (HPLC) process, a stainless steel tube, called a "column," is used to carry out the separation. Various materials can be used to fill the column, with a common filler bed material being SiO.sub.2 (silicon dioxide or silica). A mobile phase liquid is then pushed through the column under pressure. Because the bed of material (e.g., silica) within the column is very dense, the liquid must be pressurized to a relatively high-pressure (e.g., 2,000-5,000 pounds per square inch) to force the liquid through the column at an acceptable rate. A sample constituting a mixture of chemical compounds to be analyzed is then introduced into the fluid stream and enters the column. As the chemical mixture passes through the bed within the column, the different chemicals in the mixture separate from one another depending on the partition coefficients of the various constituents.
The close control of the temperature of the column is essential to detector baseline stability and retention time reproducability. Without close control of the temperature of the column, typical daily ambient air temperature fluctuations of 3.degree. to 4.degree. C. are sufficient to cause erroneous quantitation or peak misidentification, particularly in automated systems or where temperature-sensitive detectors are used. In addition, it is often desirable to heat the column above ambient temperature. Elevated column temperatures can have the benefits of shorter analysis time, more reproducible results, greater sensitivity, co-eluting peak resolution, reduced mobile phase viscosity, less system wear and improved sample solubility. Thus, temperature controlled heaters for HPLC columns are in common use. Commonly, in such heaters the HPLC column is contained in an enclosure or "oven," the temperature of which is raised to a set temperature above ambient by an electrical heating element within the enclosure. Such column heater systems may also include a preheater to preheat the mobile phase before it reaches the column. Examples of designs for such preheaters include thin walled tubes carrying the mobile phase liquid which pass through heated metal blocks or which are wound around heated posts.
In some situations, the actual temperature within the column may not be adequately regulated by controlling the temperature of the ambient air around the column within the heater enclosure. To provide more precise direct control of the temperature of the column, the column may be mounted in contact with a block of good heat conducting metal (typically aluminium) which is itself in good thermal contact with the heating element of the column heather. The column may be mounted in a groove, typically V-shaped, in the conducting block to increase the heat transfer contact area between the outside surface of the column and the heat conducting block. The block of metal acts to transfer heat to or from portions of the column to rapidly equalize the temperature of all parts of the column in addition to transfer heat to or from the column as a whole to maintain the column at the desired temperature.
One limitation of conventional heaters using heat conducting blocks is that HPLC columns come in different lengths and in different outside diameters, ranging from relatively short columns of a few centimeters (cm) in length up to 60 cm and sometimes more. A heat conducting block of a length sufficient to be in contact with a long HPLC column over substantially its entire length cannot be used with a shorter column. Thus, several heat transfer blocks, each sized to fit a particular length of HPLC column, have been required. Such prior heat conducting blocks also generally only contact a portion of the outside periphery of the HPLC columns, so that the actual heat transfer area is much less than the full available surface of the column. Further, in conventional column heaters in which the preheaters are formed on posts mounted within the temperature controlled compartment, the space allocated in the compartment for the preheater structures can limit the maximum length of the HPLC column that can be used in conjunction with preheaters.